Abstract: Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

Abstract: Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

Abstract: The technology described herein is directed to stromal-free methods of NK cell differentiation. Also described herein are cells differentiated using stromal-free methods and compositions comprising such cells. In some embodiments, the cells can be genetically modified. In some embodiments, the cells or compositions comprising said cells can be administered to a patient to treat cancer or as a cellular replacement therapy to treat a condition.

Abstract: The present invention relates generally to methods for treatment of ribosomal disorders and ribosomopathy, e.g. Diamond Blackfan anemia (DBA). In some embodiments, the invention relates to methods for the use of a small-molecule autophagy modulator for treatment of ribosomal disorders and ribosomopathy. The invention also relates to small molecule drug discovery and methods of screening compositions to determine their effectiveness for treatment of ribosomal disorders and ribosomopathies.

Abstract: The invention described herein is directed to compositions and methods for inducing red blood cell (RBC) differentiation. Additionally, provided herein are methods of treating a subject in need thereof by administering the induced RBC described herein.

Abstract: Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

Abstract: Embodiments disclosed here are production methods and compositions of engineered immune cells, such as B or T lymphocytes, from limited lineage myeloid progenitor cells, or from pluripotent stem cells, or from multilineage hematopoietic progenitor cells comprising the addition of various cell differentiation transcription factors and inhibiting epigenetic histone methylations in said cells.

Abstract: Described herein are methods of prolonging or reactivating organogenesis in a subject in need thereof (e.g., a subject that has impaired organ function such as a prematurely born infant). The methods comprise increasing the expression or activity of Lin28A or Lin28B proteins, inhibiting the expression or activity of let-7 family microRNAs, and/or inhibiting the expression or activity of Dis3L2 exonuclease.

Abstract: Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE).

Abstract: Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

Abstract: Described in the present application are methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation. In some embodiments, the methods include providing a population comprising hemogenic endothelial (HE) cells, and (i) contacting the HE cells with an amount of an agonist of transient receptor potential cation channel-subfamily vanilloid member 4 (Trpv4); and/or (ii) subjecting the cells to cyclic 2-dimensional stretching, for a time and under conditions sufficient to stimulating endothelial-to-HSC transition. Also provided herein are methods for treating subjects who have, bone marrow, metabolic, and immune diseases; the methods include administering to the subject a therapeutically effective amount of hematopoietic stem cells (HSCs) obtained by a method described herein.

Abstract: Described herein are methods of prolong or reactivating organogenesis in a subject in need thereof (e.g., a subject that has impaired organ function such as a prematurely born infant). The methods comprises increasing the expression or activity of Lin28A or Lin28B proteins, inhibiting the expression or activity of let-7 family microRNAs, and/or inhibiting the expression or activity of Dis3L2 exonuclease.

Abstract: Described herein is a LIN28-independent role of TUTases in oncogenesis. Provided herein are compositions and methods for treating cancer via inhibition of TUTases. TUTase depletion also sensitizes the cells to disruptions in RNA metabolism and/or protein metabolism. Thus, further provided herein are strategies of combination therapy, combining TUTase inhibitors, agents that disrupt RNA metabolism, and agents that disrupt protein metabolism, to treat cancer.

Abstract: Methods for preparing populations of hematopoietic stem cells (HSCs), e.g., autologous and/or allogenic HSCs, using mechanical stretching or Trpv4 agonisists, and methods of use of the HSCs in transplantation.

Abstract: The methods and kits described herein are based, in part, to the discovery of a phenotype representing a fully-reprogrammed iPS cell and several reprogramming intermediates. The methods and kits described herein permit identification of fully-reprogrammed iPS cells and further permits one of skill in the art to monitor the emergence of iPS cells during the reprogramming process. The methods/kits can also be performed using real time using live cell imaging. Also described herein are methods for screening candidate reprogramming agents by monitoring the emergence of fully-reprogrammed iPS cells in the presence and absence of such an agent.

Abstract: In one aspect, the disclosure provides methods and compositions for the production of stem cells. In one aspect, the disclosure provides methods and uses of stem cells. In some embodiments, the stem cells are induced pluripotent stem cells.

Abstract: Methods and compositions are provided for the production of stem cells and induced pluripotent stem cells, and for uses thereof.

Abstract: The methods and kits described herein are based, in part, to the discovery of a phenotype representing a fully-reprogrammed iPS cell and several reprogramming intermediates. The methods and kits described herein permit identification of fully-reprogrammed iPS cells and further permits one of skill in the art to monitor the emergence of iPS cells during the reprogramming process. The methods/kits can also be performed using real time using live cell imaging. Also described herein are methods for screening candidate reprogramming agents by monitoring the emergence of fully-reprogrammed iPS cells in the presence and absence of such an agent.

Abstract: Methods and compositions are provided for the production of stem cells and induced pluripotent stem cells, and for uses thereof.

Abstract: The methods and kits described herein are based, in part, to the discovery phenotype representing a fully-reprogrammed iPS cell and several reprogramming intermediates. The methods and kits described herein permit identification of fully-reprogrammed iPS cells and further permits one of skill in the art to monitor the emergence of iPS cells during the reprogramming process. The methods/kits can also be performed using real time using live cell imaging. Also described herein are methods for screening candidate reprogramming agents by monitoring the emergence of fully-reprogrammed iPS cells in the presence and absence of such an agent.